Potentiation by propofol of the response of rat submandibularacinar cells to purinergic agonists

Abstract

The effect of propofol (2,6-diisopropylphenol) on the intracellular concentration of calcium ([Ca2+]i) and on the response of rat submandibular acini to purinergic agonists was studied. By itself, propofol (60 to 200μM) slowly increased the [Ca2+]iwithout affecting the production of inositol phosphates. The increase of the [Ca2+]iinvolved for about 50% the mobilization of thapsigargin-sensitive intracellular calcium pools. The rest of the calcium originated from a pool distinct from mitochondria. Propofol also increased the uptake of extracellular calcium but not manganese by a mechanism inhibited by nickel. The variation of the [Ca2+]iby propofol provoked a decrease of cell volume measured by light scattering. Propofol increased the effect of a maximal concentration of extracellular ATP on the [Ca2+]i. This interaction could be observed when propofol and ATP were added simultaneously to the medium but not when propofol had been removed from the medium before adding ATP. Among ATP analogs, propofol only increased the response to benzoyl-ATP (Bz-ATP). The blockade of P2X7receptors with oxidized ATP or Coomassie blue did not prevent the interaction between propofol and ATP. The effect of propofol could also be observed even when the concentration of ATP4−was decreased by extracellular magnesium to such a level that only P2X4receptors could possibly be activated by the nucleotide. Propofol had no effect on the uptake ofmanganese, the formation of pores and the activation of phospholipase D in response to a P2X7agonist. These results exclude an interaction with this receptor.It is concluded that, in rat submandibular acini, propofol can increase the [Ca2]iand decrease the cell volume. Propofol can also modulate the activation of P2X4receptors by extracellular nucleotides. These effects are observed at concentrations of propofol reached during the induction of anesthesia and might explain why hypersalivation has been reported as one of the side-effects of propofol.